Adriana P.M. Lavrijsen

Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients

A hallmark of atopic eczema (AE) is skin barrier dysfunction. Lipids in the stratum corneum (SC), primarily ceramides, fatty acids, and cholesterol, are crucial for the barrier function, but their role in relation to AE is indistinct. Filaggrin is an epithelial barrier protein with a central role in the pathogenesis of AE. Nevertheless, the precise causes of AE-associated barrier dysfunction are largely unknown. In this study, a comprehensive analysis of ceramide composition and lipid organization in nonlesional SC of AE patients and control subjects was performed by means of mass spectrometry, infrared spectroscopy, and X-ray diffraction. In addition, the skin barrier and clinical state of the disease were examined. The level of ceramides with an extreme short chain length is drastically increased in SC of AE patients, which leads to an aberrant lipid organization and a decreased skin barrier function. Changes in SC lipid properties correlate with disease severity but are independent of filaggrin mutations. We demonstrate for the first time that changes in ceramide chain length and lipid organization are directly correlated with the skin barrier defects in nonlesional skin of AE patients. We envisage that these insights will provide a new therapeutic entry in therapy and prevention of AE.

The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients

An important feature of atopic eczema (AE) is a decreased skin barrier function. The stratum corneum (SC) lipids – comprised of ceramides (CERs), free fatty acids (FFAs) and cholesterol – fulfil a predominant role in the skin barrier function. In this clinical study, the carbon chain length distribution of SC lipids (FFAs and CERs) and their importance for the lipid organization and skin barrier function were examined in AE patients and compared with control subjects. A reduction in FFA chain length and an increase in unsaturated FFAs are observed in non‐lesional and lesional SC of AE patients. The reduction in FFA chain length associates with a reduced CER chain length, suggesting a common synthetic pathway. The lipid chain length reduction correlates with a less dense lipid organization and a decreased skin barrier function. All changes are more pronounced in lesional SC compared with non‐lesional skin. No association was observed between lipid properties and filaggrin mutations, an important predisposing factor for developing AE. The results of this study demonstrate an altered SC lipid composition and signify the importance of these changes (specifically regarding the CER and FFA chain lengths) for the impaired skin barrier function in AE. This provides insights into epidermal lipid metabolism as well as new opportunities for skin barrier repair.

Lipid to protein ratio plays an important role in the skin barrier function in patients with atopic eczema

The barrier function of the skin is primarily provided by the stratum corneum (SC), the outermost layer of the skin. Skin barrier impairment is thought to be a primary factor in the pathogenesis of atopic eczema (AE). Filaggrin is an epidermal barrier protein and common mutations in the filaggrin gene strongly predispose for AE. However, the role of filaggrin mutations in the decreased skin barrier in AE is not fully understood. It was recently shown that changes in SC lipid composition and organization play a role in the reduced skin barrier in AE.

Prevalence and risk factors of inflammatory acne vulgaris in rural and urban Ghanaian schoolchildren.

transmitted component of each re-emitted state has its own random refractive index-induced retardance (retardance is the slowing of light due to the refractive index of the structure the light is penetrating). For each colour, the interference of the selectively transmitted states, which is due to their randomized retardances, may be either constructive (which enhances the colour) or destructive (which diminishes the colour). This produces ‘interference colours’, in a process similar to that in birds’ feathers such as, for example, the peacock. Thus, all of these complex effects in combination probably produce the colours of the ‘rainbow’. Hence, the rainbow pattern is probably a luminescence phenomenon related to light in different states of polarization interacting with the superficial and ⁄or deep structural components within the lesion. Each state of polarization will suffer varying absorption and retardance, resulting in a combination of absorbance-induced and interference-induced colour. Further in-depth research is necessary in order to understand the underlying optics for such ‘rainbows’ and to assess the possible diagnostic significance.

Skin diseases among schoolchildren in Ghana, Gabon, and Rwanda

Skin diseases, especially skin infections, among schoolchildren in Africa can be a major health problem. The objective of this study was to determine the prevalences of skin diseases among children in rural and urban schools in three different African countries and to study the influence of socioeconomic level.

Electron diffraction study of lipids in non-lesional stratum corneum of atopic eczema patients

Skin barrier impairment is thought to be an important factor in the pathogenesis of atopic eczema (AE). The skin barrier is located in the stratum corneum (SC), consisting of corneocytes embedded in lipids. Ceramides, cholesterol and free fatty acids are the major lipid classes and are crucial for the skin barrier function, but their role in relation to AE is indistinct. Filaggrin is an epidermal barrier protein and common mutations in the filaggrin gene strongly predispose for AE. However, there is no strong evidence that filaggrin mutations are related to the reduced skin barrier in AE. In this study, electron diffraction is used in order to study the lipid organization of control SC and non-lesional SC of AE patients in vivo. An increased presence of the hexagonal lipid organization was observed in non-lesional SC of AE patients, indicating a less dense lipid organization. These changes correlate with a reduced skin barrier function as measured with transepidermal water loss but do not correlate with the presence of filaggrin mutations. These results are indicative for the importance of the lipid organization for a proper skin barrier function.

Point and period prevalences of eczema in rural and urban schoolchildren in Ghana, Gabon and Rwanda.

Background  Eczema is a growing problem in Africa, particularly amongst children.

A case of simultaneous primary HIV-1 and CMV infections

HIV-1 and cytomegalovirus (CMV) share common routes of transmission and most HIV-infected persons are also infected by CMV. Primary infections by HIV-1 as well as by CMV may result in similar flu-like illnesses and can also present clinically as distinct mononucleosis-like syndromes. Symptoms include fever, malaise, myalgias, arthralgias, rash, headache, lethargy, sore throat, nausea, vomiting, diarrhea, and weight loss. Although both these primary infections can cause severe symptoms, these infections often pass asymptomatically or cause only mild disease. Patients with severe disease have been described in simultaneously co-infected patients (Berger et al., 1996; Bonetti et al., 1989; Raffi et al., 1990; Schindler and Neftel, 1990). We describe a patient presenting with an acute retroviral illness directly followed by an acute primary CMV infection. This is to our knowledge the first case in which close monitoring of serological and viral load measurements have been performed. A 55-year-old previously healthy man was send to our hospital with a 3-day history of a ulcerative skin eruption, a genital ulcer, headache, sore throat, and painful inguinal lymph node enlargements. He stated having infrequent, unprotected homosexual contacts, the last contact being 4 weeks before presentation. On physical examination, the temperature was 37.3 ◦C. Painful enlarged inguinal lymph nodes were found. Examination of the skin and genitalia revealed widespread nodular and papular lesions some of which showed central hemorrhagic necrosis and ulceration. Differential diagnosis of the skin eruption was secondary syphilis, leukaemia cutis, pityriasis lichenoides et varioliformis acuta and primary HIV-1 infection. Laboratory tests revealed the following values: haemoglobin 9.5 mmol/l; WBC count 4.1 × 109/l; platelet count 86 × 109/l; serum